- Email: [email protected]
Distribution of Mediastinal Lesions Across Multi-Institutional, International, Radiology Databases
Journal Pre-proof The Distribution of Mediastinal Lesions across Multi-Institutional, International, Radiology Databases Anja C. Roden, MD, Wentao Fang, MD, Shen Yan, MD, Brett W. Carter, MD, Darin B. White, MD, Sarah M. Jenkins, MS, Grant M. Spears, Julian R. Molina, MD, PhD, Eyal Klang, MD, Mattia Di Segni, Jeanne B. Ackman, MD, Edward Z. Sanchez, MD, Nicolas Girard, MD, PhD, Engjellush Shumeri, MSc, Marie-Pierre Revel, MD, Guillaume Chassagnon, MD, Ami Rubinowitz, MD, Demetrius Dicks, MD, Frank Detterbeck, MD, Jane P. Ko, MD, Conrad Falkson, MBChB, Samantha Sigurdson, MD, Sabrina Segreto, MD, Silvana Del Vecchio, MD, Giovanella Pamieri, MD, Margaret Ottaviano, MD, Mirella Marino, MD, Robert Korst, MD, Edith M. Marom, MD PII:
S1556-0864(19)33848-1
DOI:
https://doi.org/10.1016/j.jtho.2019.12.108
Reference:
JTHO 1669
To appear in:
Journal of Thoracic Oncology
Received Date: 6 October 2019 Revised Date:
27 November 2019
Accepted Date: 3 December 2019
Please cite this article as: Roden AC, Fang W, Yan S, Carter BW, White DB, Jenkins SM, Spears GM, Molina JR, Klang E, Di Segni M, Ackman JB, Sanchez EZ, Girard N, Shumeri E, Revel M-P, Chassagnon G, Rubinowitz A, Dicks D, Detterbeck F, Ko JP, Falkson C, Sigurdson S, Segreto S, Del Vecchio S, Pamieri G, Ottaviano M, Marino M, Korst R, Marom EM, The Distribution of Mediastinal Lesions across Multi-Institutional, International, Radiology Databases, Journal of Thoracic Oncology (2020), doi: https://doi.org/10.1016/j.jtho.2019.12.108. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
1
Title: The Distribution of Mediastinal Lesions across Multi-Institutional, International,
2
Radiology Databases
3
Authors: Anja C. Roden, MD1, Wentao Fang, MD2, Shen Yan, MD3, Brett W. Carter, MD4,
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Darin B. White, MD5, Sarah M. Jenkins, MS6, Grant M. Spears6, Julian R. Molina, MD, PhD7,
5
Eyal Klang, MD8, Mattia Di Segni8, Jeanne B. Ackman, MD9, Edward Z. Sanchez, MD9, Nicolas
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Girard, MD, PhD10, Engjellush Shumeri, MSc10, Marie-Pierre Revel, MD11, Guillaume
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Chassagnon MD11, Ami Rubinowitz, MD12, Demetrius Dicks, MD12, Frank Detterbeck, MD13,
8
Jane P. Ko, MD14, Conrad Falkson, MBChB15, Samantha Sigurdson, MD15, Sabrina Segreto,
9
MD16, Silvana Del Vecchio, MD16, Giovanella Pamieri, MD17, Margaret Ottaviano, MD17,
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Mirella Marino, MD18, Robert Korst, MD19, Edith M. Marom, MD8
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1
Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, USA
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2
Department of Thoracic Surgery, Shanghai Chest Hospital, Jiaotong University Medical School,
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China
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3
Department of Radiology, Shanghai Chest Hospital, Jiaotong University Medical School, China
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4
Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center,
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Houston, Texas, USA
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5
Department of Radiology, Mayo Clinic Rochester, MN, USA
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6
Department of Health Sciences Research, Mayo Clinic Rochester, MN, USA
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7
Division of Medical Oncology, Department of Oncology; Mayo Clinic Rochester, MN, USA
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8
The Chaim Sheba Medical Center, affiliated with the Tel Aviv University, Tel Aviv, Israel
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9
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston,
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MA, USA
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10
Curie Montsouris Thorax Institute, Institute Curie, Paris, France
24
11
25
12
26
USA
27
13
Section of Thoracic Surgery, Yale University School of Medicine, New Haven, CT, USA
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14
NYU Langone Health, NYU School of Medicine, USA
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15
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16
31
17
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Naples, Naples, Italy
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18
Department of Pathology, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy.
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19
Department of Thoracic Surgery, Mount Sinai Health System, Icahn School of Medicine at
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Mount Sinai, New York, NY; Valley/Mount Sinai Comprehensive Cancer Care, Paramus, NJ;
36
Department of Surgery, The Valley Hospital, Ridgewood, NJ, USA
Radiology Department, Cochin hospital, University of Paris, Paris, France Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT,
CCSEO and Queen’s University, Kingston, Canada Department of Advanced Biomedical Sciences. University Federico II Naples, Italy
Rare Tumours Reference Center of Campania Region (CRTR), University Federico II of
37 38
Running Title: Distribution of mediastinal lesions
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Conflict of Interest Statement
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No author has a financial conflict of interest. No funding sources to disclose.
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Corresponding Author:
Anja C. Roden, MD
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Department of Laboratory Medicine & Pathology
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Mayo Clinic Rochester
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Hilton 11
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200 First St SW, Rochester MN, 55905
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Tel.:
507-284-1192
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Fax:
507-266-3771
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Email: [email protected]
50 51 52
Drs. Anja C. Roden and Wentao Fang contributed equally to the study.
Abstract
53 54
Background
55
Mediastinal lesions are uncommon; studies on their distribution are in general small and
56
from a single institution. Furthermore, these studies are usually based on pathology or surgical
57
databases and therefore miss many lesions that are not biopsied and/or resected. Our aim was to
58
identify the distribution of lesions in the mediastinum in a large international, multi-institutional
59
cohort.
60
Material and Methods
61
At each participating institution, a standardized retrospective radiology database search
62
for interpretations of CT, PET-CT and MRI scans including any of the following terms:
63
“mediastinal nodule”, “mediastinal lesion”, “mediastinal mass” or “mediastinal abnormality”
64
was performed (2011-2014). Standardized data were collected. Statistical analysis was
65
performed.
66
Results
67
Amongst 3,308 cases, thymomas (27.8%), benign mediastinal cysts (20.0%) and
68
lymphomas (16.1%) were most common. The distribution of lesions varied amongst mediastinal
69
compartments; thymomas (38.3%), benign cysts (16.8%) and neurogenic tumors (53.9%) were
70
the most common lesions in the prevascular, visceral and paravertebral mediastinum,
71
respectively (p<0.001). Mediastinal compartment was associated with age; patients with
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paravertebral lesions were the youngest (p<0.0001). Mediastinal lesions differed by
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continent/country with benign cysts being the most common mediastinal lesions in China,
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thymomas in Europe and lymphomas in North America and Israel (p<0.001). Benign cysts,
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thymic carcinomas, and metastases were more commonly seen in larger hospitals, while
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lymphomas and thymic hyperplasia occurred more often in smaller hospitals (p<0.01).
77
Conclusions
78
Our study confirmed that spectrum and frequency of mediastinal lesions depends on
79
mediastinal compartment and age. This information provides helpful demographic data and is
80
important when considering the differential diagnosis of a mediastinal lesion.
81 82 83
84
Introduction
85
Lesions of the mediastinum are rare. There have been three large imaging studies,
86
population-based cohort studies[1, 2] and a lung cancer screening study[3] which have found the
87
prevalence of mediastinal lesions to be 0.73% to 0.9%. However, the overall prevalence of
88
mediastinal lesions in an unselected population and their distribution in specific mediastinal
89
compartments are difficult to ascertain from the medical literature for various reasons.[4] First,
90
reported series usually include a defined population as they are performed for other purposes.
91
For instance the main purpose of the computed tomography (CT) imaging study by Henschke et
92
al[3] was to screen patients for lung cancer who were between 40 and 92 years old with a history
93
of 1 to 267 pack-years smoking. In the Framingham Heart Study by Araki et al[1], second and
94
third generations from the original Framingham population that were comprised of patients
95
between 30 and 62 years old and who lived in Framingham, MA, USA underwent CT scanning
96
to identify risk factors for heart disease. Second, most studies tend to include only surgically
97
resected or biopsied lesions; however, some benign lesions are never resected or even biopsied.
98
Thus, the inclusion of non-neoplastic lesions such as thymic and pericardial cysts varies between
99
series.[5-11] Third, studies tend to be centered on a single institution’s experience, which might
100
be an academic institution or a tertiary hospital, thereby introducing referral bias. In addition,
101
many series are rather small, with less than 400 cases. Fourth, there is variability in the inclusion
102
of lymphomas. While it has been previously reported that 50% of Hodgkin lymphomas (HL) and
103
20% of Non-Hodgkin lymphomas (NHL) involve the mediastinum[12], only approximately 3%
104
of HL and 6% of NHL reportedly arise as primary mediastinal malignancies.[13-15]. Finally yet
105
importantly, many of the studies on the prevalence and distribution of mediastinal lesions are
106
over 20 years old. However, the increased patient referral for imaging studies for various
107
indications and advances in imaging techniques have greatly improved the diagnostic
108
capabilities, warranting the reappraisal of the distribution of mediastinal lesions.
109
The International Thymic Malignancy Interest Group (ITMIG) started an initiative to
110
study mediastinal lesions other than thymic epithelial tumors. One of ITMIG’s goals was to
111
identify the overall frequency of different mediastinal lesions. To avoid bias introduced by
112
pathology or surgical databases that only collect cases from which tissue was recovered,
113
institutional radiology databases were explored. The aim of our study was to obtain a better
114
understanding of the frequency of solitary primary mediastinal lesions and their typical location
115
within the mediastinum and to assess if this frequency differs between geographic location
116
and/or size of the hospital, based on a search of radiology databases across multiple international
117
institutions.
118 119 120
Materials and Methods Each of the participating institutions (Table 1) conducted a standardized retrospective
121
search of their radiology database for CT, positron-emission tomography-CT (PET-CT) and
122
magnetic resonance imaging (MRI) scan interpretations performed between January 1, 2011 and
123
December 31, 2014. The search included either one of the following terms: “mediastinal
124
nodule”, “mediastinal lesion”, “mediastinal mass” or “mediastinal abnormality”. All authors
125
confirmed that only these 4 search terms were used. These terms were identified during a pilot
126
study that included four institutions (Mayo Clinic Rochester, MD Anderson Cancer Center,
127
Sheba Medical Center, Shanghai Chest Hospital) and that aimed to define optimal search criteria.
128
Because this study was carried out by investigators at multiple different institutions, the search
129
software varied and therefore no central investigator training could be carried out. The study
130
was not set up to perform search and analysis of reports independently and a sample was also not
131
tested twice.
132 133 134 135 136
The study was performed in accordance with institutional policies for the use of existing medical information for research and was approved by all local Institutional Review Boards. For subset analysis, participating institutions were categorized by size according to the number of beds (300-600, > 600). The date of the first reference of the solitary mediastinal lesion was recorded. Medical
137
records were searched for a final pathology diagnosis, date of initial scan mentioning the lesion,
138
and date of last imaging follow-up, the latter could be after December 31, 2014.
139
Based upon review of the chest CT, MRI or PET-CT report and/or images, the following
140
data were collected: (1) date of initial imaging showing the mediastinal abnormality; (2) imaging
141
modality which showed the mediastinal lesion (CT, MRI or PET-CT); (3) mediastinal
142
compartment in which the epicenter of the abnormality resided in; (4) time of follow-up of the
143
patient from first to last imaging exam; (5) diagnosis by imaging if the mass was not assessed by
144
pathology; and (6) pathology diagnosis if available. Only new diagnoses were included;
145
recurrences or duplications were excluded. The latest follow up date was June 30, 2016. While
146
lymphomas were included in the study, only primary mediastinal lymphomas that presented as a
147
solitary mediastinal lesion were considered. Patients who had mediastinal involvement by
148
systemic lymphoma and/or multiple lesions were excluded. Data on tissue sampling techniques
149
such as fine needle aspiration, core biopsy, or surgical resection were not collected. The
150
mediastinum was divided according to the ITMIG classification into prevascular, visceral, and
151
paravertebral compartments as summarized in Supplemental Table 1.[16]
152
The study population included all patients ages 18 years and older. Data on age and
153
gender were also collected. Smoking status was not noted. De-identified data were centrally
154
collected and analyzed.
155
In an attempt to identify differences in the distribution of mediastinal lesions based on
156
geographic areas, the results were combined from hospitals that were from the same continent
157
including Asia, Europe and North America, recognizing that this distribution does not entirely
158
reflect ethnicity and likely is biased by type of institution. Given the large variation in number of
159
cases contributed from the 2 hospitals in Asia, cases from China and Israel were analyzed
160
separately.
161
Data was summarized with frequencies and percentages or with medians, interquartile
162
ranges and ranges (as appropriate). Patient and lesion characteristics were compared by
163
compartment (prevascular vs visceral vs paravertebral), geographic region (China vs Israel vs
164
Europe vs North America), size of hospital (300-600 beds vs > 600 beds), age category (18-29,
165
30-39, 40-49, 50-59, 60-69, ≥ 70) and gender using Kruskal-Wallis tests for age, and Fisher’s
166
exact tests, or chi-square tests for the remaining categorical characteristics. P-values less than
167
0.05 were considered statistically significant. All analyses were performed using SAS version
168
9.4 (SAS Institute Inc., Cary, NC).
169 170 171
Results A total of 3,504 patients with a newly identified mediastinal lesion on CT, PET-CT or
172
MRI scans were identified through the multi-institutional, international database search. Of these
173
patients 196 were excluded because of lack of follow-up imaging and/or pathology. Therefore,
174
3,308 patients were available for the study. Patient demographics are summarized in Table 1.
175
Most lesions were identified by CT scan (Table 1). In approximately two-thirds of patients a
176
pathology diagnosis was available (Table 1), whereas the remainder had typical imaging findings
177
for diagnosis with imaging follow-up for confirmation.
178
Results of Pilot Study
179
To identify optimal search terms two separate pilot searches were performed on radiology
180
databases at 4 institutions. One pilot search (broad search criteria) included the following terms:
181
“mediastinal mass”, “mediastinal process”, “mediastinal abnormality”; and cases with a phrase
182
“no mediastinal mass” were excluded. CT, PET/CT and MRI studies were included. This search
183
yielded 421 (Mayo Clinic Rochester, 2012-2015), 3998 (Shanghai Chest Hospital, 2006-2015),
184
1484 (MD Anderson, 2012-2015) and 212 (Chaim Sheba, 2012-2015) cases. Between 20 and 27
185
cases were reviewed in each hospital to note possible key words; results are summarized in
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Supplemental Table 2. The other pilot search (refined search criteria) was only performed at
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Mayo Clinic Rochester using specific search terms such as “thymoma”, “thymic carcinoma”,
188
“thymolipoma”, “thymic cyst”, “germ cell tumor”, “teratoma”, “lymphangioma”, “parathyroid
189
adenoma”, “thyroid goiter”, “pericardial cyst”, “lymphoma”, “metastasis”, “esophageal cancer”,
190
“foregut cyst”, “duplication cyst”, “bronchogenic cyst”, “neurogenic tumor”, “schwannoma”,
191
“neurofibroma”, “ganglioneuroma”, “ganglioneuroblastoma”, “neuroblastoma”, “neurenteric
192
cyst”, “lateral thoracic meningocele”, “sclerosing mediastinitis”, “hemangioma”, and
193
“amyloidosis”. This search generated over 60,000 entries in 2015. This large number of cases
194
occurred because many of these lesions can occur in various organs, not only in the
195
mediastinum. While the use of the refined search criteria might have been more accurate, it was
196
felt that this approach would not have been feasible. Therefore, it was decided to use a variation
197
of the broad search criteria for the final analysis.
198
In addition a search of a pathology database was performed at Mayo Clinic Rochester
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(1995-2014) using the following search terms: “thymus”, “mediastinum”, “vertebra”, and
200
“spine”. This search identified 3,540 (thymus, mediastinum) and 5,182 (vertebra, spine) lesions.
201
Four hundred-seventy cases were reviewed of each category. The results (after exclusion of
202
metastases and duplicates) are summarized in Supplemental Table 3.
203 204 205
Overall Frequency of Different Lesions in the Mediastinum The frequency of mediastinal lesions is summarized in Table 1 and illustrated in Figure
206
1A. The entire data are tabulated in Supplemental Table 4. The most common lesions in the
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mediastinum included thymoma, which together with thymic carcinoma constituted 27.8% of
208
mediastinal lesions, benign cysts (20.0%) and lymphomas (16.1%).
209 210
Occurrence of Mediastinal Lesions Based on Mediastinal Compartment
211
Most lesions were found to reside within a single mediastinal compartment, with the
212
prevascular mediastinum being the most common site (69.8%) followed by the visceral and
213
paravertebral mediastinum (13.5% and 5.4%, respectively) (Table 1). In 370 (11.2%) patients,
214
the epicenter of the lesion could not be assessed with certainty. In these patients the lesions were
215
attributed to multiple compartments. The majority of the lesions identified in more than 1
216
compartment involved both the prevascular and the visceral compartment (299 of 370) followed
217
by lesions in the visceral and paravertebral (N=48), prevascular, visceral and paravertebral
218
(N=18) and prevascular and paravertebral (N=5) compartments. The frequency of mediastinal
219
lesions based on mediastinal compartment is summarized in Table 1 and Supplement 1. In the
220
prevascular mediastinum, thymomas (30.8%) (Figures 1A and 2A & B) were the most common
221
lesions, followed by benign cysts (24.0%) and lymphomas (14.4%). In contrast, in the visceral
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mediastinum, benign cysts (16.8%) were the predominant lesions (Figure 2C) followed by
223
metastasis (14.8%) and benign thyroid lesions (13.0%). In the paravertebral mediastinum,
224
neurogenic tumors (53.9%) (Figure 2D) were the most often identified lesions, followed by
225
benign cysts (13.9%) and lymphomas (5%).
226
Demographics of Patients Based on Location of Mediastinal Lesion
227
Patient age and gender, based on location of the mediastinal lesion, are summarized in
228
Tables 1 and 2 and Figure 1C. The mediastinal compartment in which a lesion was identified
229
was associated with the age of the patient (p<0.0001) (Table 1). Patients with lesions in the
230
paravertebral compartment were the youngest (median age, 50 years old) while patients with
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visceral mediastinal lesions were the oldest (median age, 60 years old). In contrast, there was no
232
difference in gender amongst different locations of lesions in the mediastinum.
233
Patient age was also associated with the diagnosis (Table 2). For instance, thymomas,
234
thymic carcinomas and benign cysts were most common in the age ranges of 50 to 59 and 60 to
235
69, while lymphomas and germ cell tumors were most frequently found in patients between 18
236
and 29 years old.
237
Distribution of Mediastinal Lesions Based on Geographic Region of the Hospital
238
Results of the distribution of mediastinal lesions based on geographic region are
239
summarized in Table 3 and illustrated in Figure 1B. While benign cysts were more common in
240
the group from China (35.5%), followed by thymomas and thymic carcinomas, lymphomas were
241
more common in Israel (24.1%), followed by metastases and thymomas. Metastases were overall
242
most commonly identified in cases from Israel (18.4% of all cases from Israel) (p<0.0001).
243
Cases from Europe were most commonly thymomas (22.8%), followed by lymphomas and
244
benign cysts. In North America, lymphomas were most common (25.5%), followed by
245
thymomas and benign cysts.
246
Frequency of Mediastinal Lesions Based on Size of the Hospital
247
The frequencies of mediastinal lesions based on size of the hospital are summarized in
248
Table 4. The majority of cases were contributed from larger hospitals with more than 600 beds.
249
None of the participating institutions had less than 300 beds. Relative numbers of paravertebral
250
lesions differed depending on the size of the hospital. Benign cysts, thymic carcinomas, and
251
metastases were more commonly seen in larger hospitals, while lymphomas and thymic
252
hyperplasia were found more frequently in smaller hospitals. There was no difference in the
253
relative number of patients with thymomas, neurogenic tumors, germ cell tumors, benign thyroid
254
lesions and small cell carcinomas depending on the hospital size.
255
There were significant differences between the imaging modality that was used to
256
identify the mediastinal lesion between large and smaller hospitals. Most imaging was performed
257
with CT scans. MRI and PET-CT were more frequently used in larger hospitals (4.8% and 3.1%,
258
respectively) than in smaller hospitals (1.8% and 1.2%, respectively).
259 260 261
Discussion In an international, multi-institutional study of solitary mediastinal lesions that were
262
newly identified by CT, PET-CT and/or MRI and collected over a 4-year time period by
263
radiology databases, we found that thymic epithelial malignancies (thymomas and thymic
264
carcinomas) are the most common mediastinal lesions (27.8%), followed by benign cysts
265
(20.0%), primary mediastinal lymphomas (16.1%) and metastases (5.1%). Furthermore we
266
showed that mediastinal lesions occur in the prevascular compartment most commonly, followed
267
by the visceral compartment. Thymomas were also the most common lesions in the prevascular
268
mediastinum in our study (30.8%), while benign cysts (16.8%) and neurogenic tumors (53.9%)
269
were the most commonly identified lesions in the visceral and paravertebral mediastinum,
270
respectively.
271
Our study has clinical implications, specifically because it was imaging-based and open
272
to all adult patients with any available cross-sectional chest imaging. The distribution of the
273
different mediastinal lesions found by this investigation will assist in creation of a differential
274
diagnosis when such a patient is encountered in clinic, prior to any surgical intervention or
275
pathology results. This information not only will facilitate development of an informed
276
differential diagnosis, but will also aid in initiating a logical route of continued non-invasive
277
work-up in at least a subset of these patients, justifying the use of different imaging modalities.
278
Although the frequency of mediastinal lesions has been studied in the past, the results
279
were conflicting for reasons that were mentioned earlier. It is difficult to compare our findings to
280
previous studies, as these were usually based solely on pathologic and/or surgical databases,
281
were small in size and from a single institution, and/or included cases without a final diagnosis.
282
An example as to how differences between studies substantially affect the distribution of certain
283
entities is reflected by the occurrence of a benign mediastinal cyst. In our study based on
284
radiology databases, benign mediastinal cysts were quite common; in fact, benign cysts were the
285
second most common mediastinal lesions (20.0%, after thymomas). They were the most
286
common lesions in the visceral mediastinum (16.8%), and the second most common lesions both
287
in the prevascular mediastinum (24.0%, after thymomas) and in the paravertebral mediastinum
288
(13.9%, after neurogenic tumors). Therefore, benign mediastinal cysts should be placed high on
289
the differential diagnostic list of mediastinal lesions. Similar to our study, in a study from Duke
290
University Medical Center which included 400 consecutive patients with primary mediastinal
291
lesions, all with a pathology diagnosis, 25% of patients were found to have cysts.[9] In contrast,
292
a surgical study of 37 solitary mediastinal masses found only 5 cysts (13.5%) which were
293
comprised of 3 patients with bronchogenic cysts and 2 patients with thymic cysts.[7] It is not
294
surprising that this study had a lower percentage of mediastinal cysts, as it was based on patients
295
who underwent surgical intervention. Knowing that these differences may be reflective of a
296
selection bias of a surgically treated cohort of patients as opposed to our cohort, which was based
297
on imaging studies, it is interesting when compared to two screening CT studies.[2, 3] The study
298
that aimed at screening for lung cancer[3] identified most (41 of 71 cases, 58%) mediastinal
299
lesions as “thymic masses”. Similar to our results, the vast majority of the “thymic masses” (39
300
of 41, 95%) were located in the “anterior” (prevascular) mediastinum. In that study, only 1 of the
301
41 thymic masses was identified as a cyst, 4 were found to be thymomas and 1 was diagnosed as
302
thymic carcinoma. However, in 35 patients with a “thymic mass” a specific diagnosis was not
303
made, and therefore a comparison to our study was difficult. However, in the more recent
304
screening study, which included both smokers and never-smokers, a much greater proportion of
305
benign prevascular cysts was found, more similar to our study. Of the 413 prevascular lesions
306
identified in the screening study, 50 were excised and 12 (24%) were malignant including 11
307
thymic epithelial tumors and 1 non-small-cell lung cancer. The majority of the resected lesions,
308
36 of 50 (72%), were benign cysts. Of these, 32 (89%) were thymic cysts and 4 (11%) were
309
duplication cysts. However, these results are difficult to compare to our study as the majority of
310
the lesions in this study, 362 of 413 prevascular lesions (88%), remained of unknown
311
etiology.[2] Furthermore, our data might be skewed as the majority of thymic cysts were
312
contributed from China. In fact the cohort of mediastinal lesions from China was comprised of
313
significantly more benign cysts (35.5% of all mediastinal lesions) than cohorts from Europe
314
(10.9%), Israel (10.3%), and North America (9.2%). The reason for this difference is not entirely
315
clear and might reflect, at least in part, a selection bias. This is further supported by a previous,
316
albeit much smaller, cohort of patient with mediastinal lesions from a different institution in
317
China that was identified by imaging studies and medical and surgical records and that was
318
comprised only to 15.8% of benign cysts.[17] Furthermore, conceivably, exposures and/or
319
genetic differences might also play a role. However, we did not analyze ethnicity of our study
320
cohort; therefore, these arguments are rather speculative.
321
These conflicting study results regarding the frequency of benign mediastinal cysts is of
322
no surprise, and may in fact reflect the increased use of MRI for thoracic imaging, which has
323
been increasingly recognized for its value.[18] Interestingly, MRI was most commonly used in
324
China (5.4% of all studies) which might, at least partially, explain the relatively high percentage
325
of benign mediastinal cysts in the Chinese cohort. It has been shown that benign mediastinal
326
cysts can be misinterpreted as solid on CT when they are of soft tissue attenuation on account of
327
proteinaceous or hemorrhagic content (up to 97 Hounsfield Units) despite containing fluid alone,
328
which has led in the past to unnecessary surgical resection.[2, 19] It could be that many of the
329
undiagnosed mediastinal masses found in screening for lung cancer patients[3] may have
330
represented such high attenuation cysts. It is possible that the occurrence of mediastinal cysts is
331
far higher than that suggested by our investigation, given the not infrequent under-recognition on
332
CT and the continued underutilization of MRI in many parts of the world. The fact that the use
333
of MRI imaging for chest evaluation has been lagging behind other parts of the body, is only in
334
part due to the motion artifacts inherit to the chest. These artifacts can be overcome with
335
different techniques routinely used today. Reaching clinical decisions by CT images alone,
336
without using MRI, has resulted in many unnecessary surgical procedures for benign disease.[19]
337
The increased use of MRI for evaluation of mediastinal masses is most pronounced in large
338
medical centers, where some clinicians and radiologists with a specific interest in thymomas and
339
MRI, work. Indeed, we noted higher utilization rates of thoracic MRI in larger medical centers as
340
compared to smaller hospitals (4.8% vs 1.8%, respectively). Another explanation might be that
341
MRI scanners are more numerous and more readily accessible in larger centers. Our findings
342
further emphasize that single institution studies might harbor a bias for certain mediastinal
343
lesions, depending on the size of the hospital.
344
We also showed that the occurrence of mediastinal lesions differs with age. For instance,
345
while thymomas, thymic carcinomas, benign cysts, metastases and small cell carcinomas were
346
more commonly identified in patients 50 years and older, lymphomas, germ cell tumors and
347
neurogenic tumors were more often found in patients younger than 50 years old. In fact,
348
lymphomas and germ cell tumors were most commonly seen in patients who were less than 30
349
years old. These findings confirmed previous observations that show median ages of 56[20] and
350
59.6[21] years for thymomas and thymic carcinomas, respectively but a mean age of 29
351
years[22] for mediastinal germ cell tumors.
352
In an attempt to analyze whether certain mediastinal lesions are more commonly seen in
353
larger hospitals, we stratified our results based on the number of beds. As mediastinal lesions are
354
overall rare, it was not surprising that most patients were contributed from larger hospitals with
355
more than 600 beds. None of the participating institutions had less than 300 beds. While this
356
could reflect participation bias, it might also show that these patients were commonly referred to
357
larger hospitals with more expertise in treating these patients.
358
We also showed that the frequency of mediastinal lesions differs depending on the
359
region. While in our study the most common mediastinal lesions overall were thymomas,
360
lymphomas were actually the predominant lesions amongst cases contributed from North
361
America (25.5%) and Israel (24.1%). Furthermore, in China, the relative number of prevascular
362
lesions (83.5%) was higher than in Europe (62.5%), North America (60.8%), and Israel (51.7%),
363
while visceral lesions were much less common in China (5.2%) than in Israel (26.4%), Europe
364
(21.9%) or North America (17.8%). While these findings might be due to referral bias, as all of
365
the cases from China and Israel were contributed from a single hospital, respectively, ethnic
366
differences might also play a role. For instance a study including immigrants with myasthenia
367
gravis in northern Europe showed that myasthenia gravis with thymoma was more frequent in
368
Asian myasthenia gravis immigrants compared with immigrants from Europe and South
369
America.[23] That study concluded that Asian immigrants (in that study from Indonesia, China,
370
Thailand, Vietnam, India, Turkey, Iran, Iraq, and Pakistan) with myasthenia gravis might carry
371
genetic factors or environmental/lifestyle factors that contribute to their specific phenotype.
372
However, we have not collected data specifically on ethnicity from our patients, therefore, a firm
373
conclusion with regards to differences in the frequency of mediastinal lesions based on ethnicity
374
cannot be drawn from our results.
375
While some studies of the incidence of mediastinal lesions avoid the inclusion of
376
lymphomas, our study indicated that lymphomas can occur as a newly diagnosed, single, discrete
377
lesion in the mediastinum. This of course was not reflected in lung cancer screening studies, as
378
such patients do not meet the criteria of inclusion for lung cancer screening studies.[3] Our data
379
highlighted that lymphomas need to be considered in the differential diagnosis of solitary
380
mediastinal lesions. In fact, we showed that lymphomas are the third most common lesion in the
381
mediastinum (16.1%) and although lymphomas can occur in any compartment, these tumors
382
were most often found in the prevascular mediastinum (14.4%) where they represented the third
383
most common lesion after thymomas and benign cysts. Interestingly, lymphomas were most
384
commonly identified in patients from North America (25.5%), followed by Israel (24.1%) and
385
Europe (16.6%) and only 4.9% of all patients from China had lymphomas. Again, the reason for
386
that difference is not clear, and we did not check ethnicity of patients in our study. However, it is
387
known that there are global variations in the incidence of lymphoma. For example, there are
388
marked variations in the incidence rates of NHL in various world regions with Israel Jews having
389
the highest incidence rate of NHL followed by Australia, USA whites, Canada, and Portugal in a
390
recent study of 185 countries using the GLOBOCAN database.[24]
391
There are limitations to our study. (i) Although our study is a multi-institutional,
392
international effort, it solely gathered data from China, Israel, Europe and North America, and
393
lacked contributions from South America, Africa and Australia. Furthermore, a large variety of
394
ethnic groups exist within some of the hospitals studied, in particularly in Europe and North
395
America which could not be assessed due to the retrospective nature of the study. (ii) While over
396
two-thirds of cases had a diagnosis established by pathology, a diagnosis of the remaining
397
patients was established based on imaging investigation and follow-up. (iii) Only lymphomas
398
that presented as a single dominant mediastinal lesion were included, however, conceivably,
399
some of these could have presented as mediastinal involvement by a systemic disease, in a region
400
not included in the imaging study. (iv) The search was performed using the aforementioned 4
401
broad search criteria. The use of these mandated search terms instead of a the refined word
402
search to report lesions may have caused some lesions to escape detection. However, as
403
identified during the pilot study, using refined search terms would have been impractical. (v).
404
While medical records were reviewed for follow-up information and pathology reports,
405
techniques that were used to retrieve the tissue such as FNA, core biopsies or resection was not
406
noted. Therefore, it is difficult to estimate whether potentially pathologic diagnoses could have
407
been missed due to sampling bias in FNAs and core biopsies.
408
Taken together, our multi-institutional, international study of solitary mediastinal lesions
409
based on radiology databases provides an important reference for the frequency and distribution
410
of mediastinal lesions identified on cross-sectional imaging including variance with patient age
411
and geographic region. This information is important when considering the differential diagnosis
412
of a specific patient.
413 414
References
415 416
1.
417 418
Study: Prevalence and CT Image Characteristics. Eur J Radiol Open 2015, 2:26-31. 2.
419 420
Araki T, Nishino M, Gao W, et al: Anterior Mediastinal Masses in the Framingham Heart
Yoon SH, Choi SH, Kang CH, Goo JM: Incidental Anterior Mediastinal Nodular Lesions on Chest CT in Asymptomatic Subjects. J Thorac Oncol 2018, 13:359-366.
3.
Henschke CI, Lee IJ, Wu N, Farooqi A, Khan A, Yankelevitz D, Altorki NK: CT
421
screening for lung cancer: prevalence and incidence of mediastinal masses. Radiology
422
2006, 239:586-590.
423
4.
de Jong WK, Blaauwgeers JL, Schaapveld M, Timens W, Klinkenberg TJ, Groen HJ:
424
Thymic epithelial tumours: a population-based study of the incidence, diagnostic
425
procedures and therapy. Eur J Canc 2008, 44:123-130.
426
5.
Adegboye VO, Brimmo AI, Adebo OA, Ogunseyinde OO, Obajimi MO: The place of
427
clinical features and standard chest radiography in evaluation of mediastinal masses.
428
West Afr J Med 2003, 22:156-160.
429
6.
430 431
Presentation of primary mediastinal masses in Ibadan. East Afr Med J 2003, 80:484-487. 7.
432 433
Adegboye VO, Ogunseyinde AO, Obajimi MO, Ogunbiyi O, Brimmo AI, Adebo OA:
Alizzi AM, Hemli JM, Diqer AM, Bidstrup B: Primary solitary mediastinal mass lesions: a review of 37 cases. Heart Lung Circ 2006, 15:310-313.
8.
Azarow KS, Pearl RH, Zurcher R, Edwards FH, Cohen AJ: Primary mediastinal masses.
434
A comparison of adult and pediatric populations. J Thorac Cardiovasc Surg 1993,
435
106:67-72.
436
9.
Davis RD, Jr., Oldham HN, Jr., Sabiston DC, Jr.: Primary cysts and neoplasms of the
437
mediastinum: recent changes in clinical presentation, methods of diagnosis, management,
438
and results. Ann Thorac Surg 1987, 44:229-237.
439
10.
440 441
of bronchogenic cysts between adults and children. J Pediatr Surg 2015, 50:399-401. 11.
442 443
12.
448
Petersdorf s: Mediastinal lymphomas. In Mediastinal Tumors: Update 1995. Edited by Wood de, Thomas CRJ. New York: Springer-Verlag; 1995
13.
446 447
Rubush JL, Gardner IR, Boyd WC, Ehrenhaft JL: Mediastinal tumors. Review of 186 cases. J Thorac Cardiovasc Surg 1973, 65:216-222.
444 445
Jiang JH, Yen SL, Lee SY, Chuang JH: Differences in the distribution and presentation
Johnson DW, Hoppe RT, Cox RS, Rosenberg SA, Kaplan HS: Hodgkin's disease limited to intrathoracic sites. Cancer 1983, 52:8-13.
14.
Levitt LJ, Aisenberg AC, Harris NL, Linggood RM, Poppema S: Primary non-Hodgkin's lymphoma of the mediastinum. Cancer 1982, 50:2486-2492.
449
15.
450 451
Primary mediastinal lymphoma in adults. Am J Med 1980, 68:509-514. 16.
452 453
Lichtenstein AK, Levine A, Taylor CR, Boswell W, Rossman S, Feinstein DI, Lukes RJ:
Carter BW, Tomiyama N, Bhora FY, et al: A modern definition of mediastinal compartments. J Thorac Oncol 2014, 9:S97-101.
17.
Liu T, Al-Kzayer LFY, Xie X, Fan H, Sarsam SN, Nakazawa Y, Chen L: Mediastinal
454
lesions across the age spectrum: a clinicopathological comparison between pediatric and
455
adult patients. Oncotarget 2017, 8:59845-59853.
456
18.
Ackman JB, Gaissert HA, Lanuti M, Digumarthy SR, Shepard JA, Halpern EF, Wright
457
CD: Impact of Nonvascular Thoracic MR Imaging on the Clinical Decision Making of
458
Thoracic Surgeons: A 2-year Prospective Study. Radiology 2016, 280:464-474.
459
19.
Ackman JB, Verzosa S, Kovach AE, Louissaint A, Jr., Lanuti M, Wright CD, Shepard
460
JA, Halpern EF: High rate of unnecessary thymectomy and its cause. Can computed
461
tomography distinguish thymoma, lymphoma, thymic hyperplasia, and thymic cysts? Eur
462
J Radiol 2015, 84:524-533.
463
20.
Roden AC, Yi ES, Jenkins SM, et al: Modified Masaoka stage and size are independent
464
prognostic predictors in thymoma and modified Masaoka stage is superior to
465
histopathologic classifications. J Thorac Oncol 2015, 10:691-700.
466
21.
Roden AC, Yi ES, Cassivi SD, Jenkins SM, Garces YI, Aubry MC: Clinicopathological
467
features of thymic carcinomas and the impact of histopathological agreement on
468
prognostical studies. Eur J Cardiothorac Surg 2013, 43:1131-1139.
469
22.
Stang A, Trabert B, Wentzensen N, Cook MB, Rusner C, Oosterhuis JW, McGlynn KA:
470
Gonadal and extragonadal germ cell tumours in the United States, 1973-2007. Int J
471
Androl 2012, 35:616-625.
472
23.
473 474
Boldingh MI, Maniaol A, Brunborg C, et al: Prevalence and clinical aspects of immigrants with myasthenia gravis in northern Europe. Muscle Nerve 2016.
24.
Miranda-Filho A, Pineros M, Znaor A, Marcos-Gragera R, Steliarova-Foucher E, Bray F:
475
Global patterns and trends in the incidence of non-Hodgkin lymphoma. Cancer Causes
476
Control 2019, 30:489-499.
477 478 479 480
Figure Legends:
481
Figure 1:
482
compartments. “Other” compartments include lesions that were located in more than one
483
compartment including prevascular and visceral, visceral and paravertebral, prevascular, visceral
484
and paravertebral, and prevascular and paravertebral. Distribution of the most common
485
mediastinal lesions based on geographic areas (B) and age (C). “Other” diagnoses include all
486
diagnoses that are listed in Table 3 except thymoma, benign cyst, lymphoma, thymic carcinoma,
487
and metastasis.
488
Figure 2:
489
in a 53-year-old woman followed for a remote history of Hodgkin lymphoma. A. Contrast
490
enhanced chest CT at the level of the transverse aorta (A) demonstrates a heterogeneous mass
491
(M) in the prevascular mediastinum directly invading the superior vena cava (arrow). B. Fused
492
positron emission tomography–computed tomography (PET-CT) shows there is 68gallium-
493
labelled somatostatin analogue in the mass. C. Esophageal duplication cyst in a 62-year old
494
woman. Unenhanced chest CT shows a 3.7cm homogenous intermediate attenuation mass
495
(arrow) at the level of the left atrium (LA) abutting the esophagus (arrowhead). D. Schwannoma
A. Distribution of the most common mediastinal lesions throughout the different
Example of common mediastinal lesions. A, B. WHO type B2 stage III thymoma
496
in a 34-year old woman. T2 weighted MR image at the level of the sterno-clavicular joint (S)
497
shows a high intensity mass (M) in the paravertebral mediastinum extending into the
498
intervertebral neural foramina (arrow).
499 500
Acknowledgements: Dr. Anja C. Roden would like to thank Robert Dominick for his work on
501
the radiology database.
Table 1: Distribution of mediastinal lesions based on mediastinal compartment (N=3,308)
Mediastinal Compartment, N (%)a
Overall, N (%)
Prevascular
Visceral
Paravertebral
pValuee
N
%
N
%
N
%
N
%
Number of patients
3,308
2,310
446
180
Age in years, median (Q1, Q3)
54.0
54.0
60.0
50.0
(range)
(40.0, 65.0) (40.0, 64.1) (48.0, 70.0) (36.0, 61.0) (18-98)
Gender, maleb
<0.0001
(18-98)
(18-98)
1,676 50.7 1164 50.4 225 50.6
(18-89)
49.4
0.97
92.4 2145 92.9 407 91.3 165 91.7
0.45
89
Imaging modalityf CT
3058
MRI
150
4.5
97
4.2
22
4.9
12
6.7
PET-CT
96
2.9
66
2.9
17
3.8
3
1.7
Pathology diagnosis availablec
2256 68.3 1503 65.1 309 69.4 124 69.3
0.14
Mediastinal lesiond Thymoma
734
22.2
712 30.8
7
1.6
0
0.0
Benign cyst
661
20.0
553 24.0
75
16.8
25
13.9 <0.0001
Lymphoma
532
16.1
333 14.4
34
7.6
9
5.0
<0.0001
Thymic carcinoma
186
5.6
172
1
0.2
0
0.0
<0.0001
7.5
<0.0001
Metastasis
168
5.1
64
2.8
66
14.8
4
2.2
<0.0001
Neurogenic tumor
136
4.1
24
1.0
5
1.1
97
53.9
<0.0001
Germ cell tumor
134
4.1
116
5.0
1
0.2
2
1.1
<0.0001
Benign thyroid lesion
120
3.6
40
1.7
58
13.0
0
0.0
<0.0001
Thymic hyperplasia
91
2.8
90
3.9
0
0.0
0
0.0
<0.0001
Small cell carcinoma
67
2.0
10
0.4
32
7.2
0
0.0
<0.0001
Other
476
14.4
194
8.4
167 37.4
43
23.9
Institutions (by continent and in alphabetical order; size [300-600 beds vs
N
%
1,323
40.0
87
2.6
Hospices Civils de Lyon, France (300-600)
233
7.0
Hôpital Cochin, Paris, France (>600)
164
5.0
Università Degli Studi di Napoli Federico II, Napoli, Italy (>600)
24
0.7
Kingston General Hospital, Ontario, Canada (300-600)
94
2.8
Massachusetts General Hospital, Boston MA, USA (>600)
506
15.3
Mayo Clinic, Rochester MN, USA (>600)
293
8.9
MD Anderson Cancer Center, Houston TX, USA (>600)
337
10.2
NYU Langone Medical Center, New York NY, USA (>600)
120
3.6
Yale School of Medicine, New Haven CT, USA (>600)
127
3.8
>600 beds] is in parentheses) Asia Shanghai Chest Hospital, China (>600) Sheba Medical Center, Ramat Gan, Israel (>600) Europe
North America
Information not available in a2 cases, b1 case, c5 cases, d3 cases, ep-value reflects only difference between prevascular, visceral and paravertebral compartments, Fisher Exact test used for all pvalues except for age for which Kruskal Wallis test was used, f4 other modalities reported besides CT, MRI, PET; these modalities are not included in this table; fields in red mark the entity that is most common in the respective mediastinal compartment.
Table 2: Distribution of mediastinal lesions based on age (N=3,308) p-value a
Age Category (in years) 18-29 N
%b
N
Number of patients
30-39 N
401
Gender, malec
%
40-49 N
424
%
50-59 N
534
%
60-69 N
714
%
≥70 N
681
% 554
221
55.1
232
54.7
254
47.6
336
47.1
356
52.3
277
50
0.029
Mediastinal lesion, N (%)d Thymoma
734
29
7.3
62
14.7
122
22.9
194
27.2
177
26.0
150
27.1 <0.0001
Benign cyst
661
16
4.0
60
14.2
109
20.5
186
26.1
164
24.1
126
22.7 <0.0001
Lymphoma
532
176
44.0 122
28.8
87
16.3
53
7.4
51
7.5
43
7.8
<0.0001
Thymic carcinoma
186
12
3.0
22
5.2
27
5.1
49
6.9
51
7.5
25
4.5
0.020
Metastasis
168
7
1.8
18
4.3
27
5.1
37
5.2
41
6.0
38
6.9
0.012
Neurogenic tumor
136
20
5.0
25
5.9
22
4.1
33
4.6
25
3.7
11
2.0
0.044
Germ cell tumor
134
65
16.3
42
9.9
15
2.8
8
1.1
3
0.4
1
0.2
<0.0001
Benign thyroid lesion
120
1
0.3
3
0.7
9
1.7
23
3.2
33
4.8
51
9.2
<0.0001
Thymic hyperplasia
91
24
6.0
17
4.0
27
5.1
15
2.1
7
1.0
1
0.2
<0.0001
Small cell carcinoma
67
0
0.0
1
0.2
4
0.8
16
2.2
25
3.7
21
3.8
<0.0001
Other
476
50
12.5
51
12.0
84
15.7
100
14.0
104
15.3
87
15.7
a
Chi-Square test; bpercentages are based on column; Information not available in c1 case, d3 cases
Table 3: Distribution of mediastinal lesions based on geographic region (N=3,308) P-Valuea
Geographic region, N (%) China
Israel
N
%
Europe
N
%
N
North America %
N
%
Number of patients
1,323
87
421
1,477
Age in years, median (Q1, Q3) (range)
55.0
53.0
53.3
53.0
(42.0, 64.0)
(34.0, 67.0)
(36.2, 65.2)
(39.0, 66.0)
(18-98)
(21-98)
(18-97.1)
(18-95.9)
Gender, male, N (%)b
0.70
678
51.2
45
52.3
207
49.2
746
50.5
0.88
1250
94.5
75
86.2
400
95.0
1333
90.3
<0.0001
MRI
72
5.4
2
2.3
9
2.1
67
4.5
PET-CT
0
0
10
11.5
12
2.9
74
5.0
691
52.3
50
57.5
353
83.8
1162
78.9
Imaging Modality, N (%) CT
Pathology diagnosis available, N (%)c Mediastinal compartment, N (%)d
<0.0001
Prevascular
1105
83.5
45
51.7
263
62.5
897
60.8
<0.0001
Visceral
69
5.2
23
26.4
92
21.9
262
17.8
<0.0001
Paravertebral
84
6.3
1
1.1
29
6.9
66
4.5
0.02
Multiple compartmentsf
65
4.9
18
20.7
37
8.8
250
16.9
<0.0001
Thymoma
424
32.0
11
12.6
96
22.8
203
13.8
<0.0001
Benign cyst
470
35.5
9
10.3
46
10.9
136
9.2
<0.0001
Lymphoma
65
4.9
21
24.1
70
16.6
376
25.5
<0.0001
Thymic carcinoma
106
8.0
7
8.0
14
3.3
59
4.0
<0.0001
Metastasis
3
0.2
16
18.4
19
4.5
130
8.8
<0.0001
Neurogenic tumor
84
6.3
0
0
16
3.8
36
2.4
<0.0001
Germ cell tumor
72
5.4
1
1.1
8
1.9
53
3.6
0.003
Benign thyroid lesion
29
2.2
2
2.3
13
3.1
76
5.2
0.0004
Thymic hyperplasia
0
0
3
3.4
35
8.3
53
3.6
<0.0001
Small cell carcinoma
1
0.1
2
2.3
5
1.2
59
4.0
<0.0001
Mediastinal lesion, N (%)e
Other a
69
5.2
15
17.2
99
23.5
293
19.8
<0.0001
Fisher Exact or Chi-square test for all except age (Kruskal Wallis test); Information not available in b1 case, c5 cases, d2 cases, e3
cases; fMultiple compartments: Tumors that were present in more than one compartment. See supplement 1 for entire list of tumors; fields in red mark the entity that is most common in the respective mediastinal compartment.
Table 4: Distribution of mediastinal lesions based on size of hospital and type of institution (N=3,308) Size of hospital, N (%) N of Beds 300-600 N
>600 %
p-value
N
%
Number of patients
327
2,981
Age in years, median (Q1, Q3)
52.4
54.0
(34.0, 66.8)
(40.0, 65.0)
(18-97.1)
(18-98)
(range)
Gender, male, N (%)a
0.12e
154
47.1
1,522
51.1
0.18f
317
96.9
2741
91.9
0.011f
MRI
6
1.8
144
4.8
PET-CT
4
1.2
92
3.1
293
89.6
1963
66.0
<0.0001f
Prevascular
215
65.7
2095
70.3
0.10f
Visceral
55
16.8
391
13.1
0.073f
Paravertebral
28
8.6
152
5.1
0.014f
Multiple compartmentsh
29
8.9
341
11.4
Imaging modality, N (%)g CT
Pathology diagnosis available, N (%)b Mediastinal compartment, N (%)c
Mediastinal lesion, N (%)d Thymoma
75
22.9
659
22.1
0.73f
Benign cyst
28
8.6
633
21.3
<0.0001f
Lymphoma
72
22.0
460
15.4
0.0032f
Thymic carcinoma
6
1.8
180
6.0
0.0009f
Metastasis
5
1.5
163
5.5
0.0008f
Neurogenic tumor
8
2.4
128
4.3
0.14f
Germ cell tumor
9
2.8
125
4.2
0.24f
Benign thyroid lesion
14
4.3
106
3.6
0.53f
Thymic hyperplasia
18
5.5
73
2.5
0.0036f
Small cell carcinoma
2
0.6
65
2.2
0.060f
Others
90
27.5
386
12.9
Information not available in a1 case, b5 cases, c2 cases; d3 cases, eKruskal Wallis test, fFisher Exact test, gOther imaging modality in 4 cases in institutions with >600 beds; hMultiple compartments: Tumors that were present in more than one compartment. See supplement 1 for entire list of tumors; fields in red mark the entity that is most common in the respective mediastinal compartment.
S1556-0864(19)33848-1
DOI:
https://doi.org/10.1016/j.jtho.2019.12.108
Reference:
JTHO 1669
To appear in:
Journal of Thoracic Oncology
Received Date: 6 October 2019 Revised Date:
27 November 2019
Accepted Date: 3 December 2019
Please cite this article as: Roden AC, Fang W, Yan S, Carter BW, White DB, Jenkins SM, Spears GM, Molina JR, Klang E, Di Segni M, Ackman JB, Sanchez EZ, Girard N, Shumeri E, Revel M-P, Chassagnon G, Rubinowitz A, Dicks D, Detterbeck F, Ko JP, Falkson C, Sigurdson S, Segreto S, Del Vecchio S, Pamieri G, Ottaviano M, Marino M, Korst R, Marom EM, The Distribution of Mediastinal Lesions across Multi-Institutional, International, Radiology Databases, Journal of Thoracic Oncology (2020), doi: https://doi.org/10.1016/j.jtho.2019.12.108. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
1
Title: The Distribution of Mediastinal Lesions across Multi-Institutional, International,
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Radiology Databases
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Authors: Anja C. Roden, MD1, Wentao Fang, MD2, Shen Yan, MD3, Brett W. Carter, MD4,
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Darin B. White, MD5, Sarah M. Jenkins, MS6, Grant M. Spears6, Julian R. Molina, MD, PhD7,
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Eyal Klang, MD8, Mattia Di Segni8, Jeanne B. Ackman, MD9, Edward Z. Sanchez, MD9, Nicolas
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Girard, MD, PhD10, Engjellush Shumeri, MSc10, Marie-Pierre Revel, MD11, Guillaume
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Chassagnon MD11, Ami Rubinowitz, MD12, Demetrius Dicks, MD12, Frank Detterbeck, MD13,
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Jane P. Ko, MD14, Conrad Falkson, MBChB15, Samantha Sigurdson, MD15, Sabrina Segreto,
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MD16, Silvana Del Vecchio, MD16, Giovanella Pamieri, MD17, Margaret Ottaviano, MD17,
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Mirella Marino, MD18, Robert Korst, MD19, Edith M. Marom, MD8
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1
Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, USA
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2
Department of Thoracic Surgery, Shanghai Chest Hospital, Jiaotong University Medical School,
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China
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3
Department of Radiology, Shanghai Chest Hospital, Jiaotong University Medical School, China
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4
Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center,
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Houston, Texas, USA
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5
Department of Radiology, Mayo Clinic Rochester, MN, USA
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6
Department of Health Sciences Research, Mayo Clinic Rochester, MN, USA
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7
Division of Medical Oncology, Department of Oncology; Mayo Clinic Rochester, MN, USA
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8
The Chaim Sheba Medical Center, affiliated with the Tel Aviv University, Tel Aviv, Israel
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9
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston,
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MA, USA
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10
Curie Montsouris Thorax Institute, Institute Curie, Paris, France
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11
25
12
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USA
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13
Section of Thoracic Surgery, Yale University School of Medicine, New Haven, CT, USA
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14
NYU Langone Health, NYU School of Medicine, USA
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15
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16
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17
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Naples, Naples, Italy
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18
Department of Pathology, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy.
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19
Department of Thoracic Surgery, Mount Sinai Health System, Icahn School of Medicine at
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Mount Sinai, New York, NY; Valley/Mount Sinai Comprehensive Cancer Care, Paramus, NJ;
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Department of Surgery, The Valley Hospital, Ridgewood, NJ, USA
Radiology Department, Cochin hospital, University of Paris, Paris, France Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT,
CCSEO and Queen’s University, Kingston, Canada Department of Advanced Biomedical Sciences. University Federico II Naples, Italy
Rare Tumours Reference Center of Campania Region (CRTR), University Federico II of
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Running Title: Distribution of mediastinal lesions
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Conflict of Interest Statement
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No author has a financial conflict of interest. No funding sources to disclose.
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Corresponding Author:
Anja C. Roden, MD
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Department of Laboratory Medicine & Pathology
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Mayo Clinic Rochester
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Hilton 11
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200 First St SW, Rochester MN, 55905
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Tel.:
507-284-1192
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Fax:
507-266-3771
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Email: [email protected]
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Drs. Anja C. Roden and Wentao Fang contributed equally to the study.
Abstract
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Background
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Mediastinal lesions are uncommon; studies on their distribution are in general small and
56
from a single institution. Furthermore, these studies are usually based on pathology or surgical
57
databases and therefore miss many lesions that are not biopsied and/or resected. Our aim was to
58
identify the distribution of lesions in the mediastinum in a large international, multi-institutional
59
cohort.
60
Material and Methods
61
At each participating institution, a standardized retrospective radiology database search
62
for interpretations of CT, PET-CT and MRI scans including any of the following terms:
63
“mediastinal nodule”, “mediastinal lesion”, “mediastinal mass” or “mediastinal abnormality”
64
was performed (2011-2014). Standardized data were collected. Statistical analysis was
65
performed.
66
Results
67
Amongst 3,308 cases, thymomas (27.8%), benign mediastinal cysts (20.0%) and
68
lymphomas (16.1%) were most common. The distribution of lesions varied amongst mediastinal
69
compartments; thymomas (38.3%), benign cysts (16.8%) and neurogenic tumors (53.9%) were
70
the most common lesions in the prevascular, visceral and paravertebral mediastinum,
71
respectively (p<0.001). Mediastinal compartment was associated with age; patients with
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paravertebral lesions were the youngest (p<0.0001). Mediastinal lesions differed by
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continent/country with benign cysts being the most common mediastinal lesions in China,
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thymomas in Europe and lymphomas in North America and Israel (p<0.001). Benign cysts,
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thymic carcinomas, and metastases were more commonly seen in larger hospitals, while
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lymphomas and thymic hyperplasia occurred more often in smaller hospitals (p<0.01).
77
Conclusions
78
Our study confirmed that spectrum and frequency of mediastinal lesions depends on
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mediastinal compartment and age. This information provides helpful demographic data and is
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important when considering the differential diagnosis of a mediastinal lesion.
81 82 83
84
Introduction
85
Lesions of the mediastinum are rare. There have been three large imaging studies,
86
population-based cohort studies[1, 2] and a lung cancer screening study[3] which have found the
87
prevalence of mediastinal lesions to be 0.73% to 0.9%. However, the overall prevalence of
88
mediastinal lesions in an unselected population and their distribution in specific mediastinal
89
compartments are difficult to ascertain from the medical literature for various reasons.[4] First,
90
reported series usually include a defined population as they are performed for other purposes.
91
For instance the main purpose of the computed tomography (CT) imaging study by Henschke et
92
al[3] was to screen patients for lung cancer who were between 40 and 92 years old with a history
93
of 1 to 267 pack-years smoking. In the Framingham Heart Study by Araki et al[1], second and
94
third generations from the original Framingham population that were comprised of patients
95
between 30 and 62 years old and who lived in Framingham, MA, USA underwent CT scanning
96
to identify risk factors for heart disease. Second, most studies tend to include only surgically
97
resected or biopsied lesions; however, some benign lesions are never resected or even biopsied.
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Thus, the inclusion of non-neoplastic lesions such as thymic and pericardial cysts varies between
99
series.[5-11] Third, studies tend to be centered on a single institution’s experience, which might
100
be an academic institution or a tertiary hospital, thereby introducing referral bias. In addition,
101
many series are rather small, with less than 400 cases. Fourth, there is variability in the inclusion
102
of lymphomas. While it has been previously reported that 50% of Hodgkin lymphomas (HL) and
103
20% of Non-Hodgkin lymphomas (NHL) involve the mediastinum[12], only approximately 3%
104
of HL and 6% of NHL reportedly arise as primary mediastinal malignancies.[13-15]. Finally yet
105
importantly, many of the studies on the prevalence and distribution of mediastinal lesions are
106
over 20 years old. However, the increased patient referral for imaging studies for various
107
indications and advances in imaging techniques have greatly improved the diagnostic
108
capabilities, warranting the reappraisal of the distribution of mediastinal lesions.
109
The International Thymic Malignancy Interest Group (ITMIG) started an initiative to
110
study mediastinal lesions other than thymic epithelial tumors. One of ITMIG’s goals was to
111
identify the overall frequency of different mediastinal lesions. To avoid bias introduced by
112
pathology or surgical databases that only collect cases from which tissue was recovered,
113
institutional radiology databases were explored. The aim of our study was to obtain a better
114
understanding of the frequency of solitary primary mediastinal lesions and their typical location
115
within the mediastinum and to assess if this frequency differs between geographic location
116
and/or size of the hospital, based on a search of radiology databases across multiple international
117
institutions.
118 119 120
Materials and Methods Each of the participating institutions (Table 1) conducted a standardized retrospective
121
search of their radiology database for CT, positron-emission tomography-CT (PET-CT) and
122
magnetic resonance imaging (MRI) scan interpretations performed between January 1, 2011 and
123
December 31, 2014. The search included either one of the following terms: “mediastinal
124
nodule”, “mediastinal lesion”, “mediastinal mass” or “mediastinal abnormality”. All authors
125
confirmed that only these 4 search terms were used. These terms were identified during a pilot
126
study that included four institutions (Mayo Clinic Rochester, MD Anderson Cancer Center,
127
Sheba Medical Center, Shanghai Chest Hospital) and that aimed to define optimal search criteria.
128
Because this study was carried out by investigators at multiple different institutions, the search
129
software varied and therefore no central investigator training could be carried out. The study
130
was not set up to perform search and analysis of reports independently and a sample was also not
131
tested twice.
132 133 134 135 136
The study was performed in accordance with institutional policies for the use of existing medical information for research and was approved by all local Institutional Review Boards. For subset analysis, participating institutions were categorized by size according to the number of beds (300-600, > 600). The date of the first reference of the solitary mediastinal lesion was recorded. Medical
137
records were searched for a final pathology diagnosis, date of initial scan mentioning the lesion,
138
and date of last imaging follow-up, the latter could be after December 31, 2014.
139
Based upon review of the chest CT, MRI or PET-CT report and/or images, the following
140
data were collected: (1) date of initial imaging showing the mediastinal abnormality; (2) imaging
141
modality which showed the mediastinal lesion (CT, MRI or PET-CT); (3) mediastinal
142
compartment in which the epicenter of the abnormality resided in; (4) time of follow-up of the
143
patient from first to last imaging exam; (5) diagnosis by imaging if the mass was not assessed by
144
pathology; and (6) pathology diagnosis if available. Only new diagnoses were included;
145
recurrences or duplications were excluded. The latest follow up date was June 30, 2016. While
146
lymphomas were included in the study, only primary mediastinal lymphomas that presented as a
147
solitary mediastinal lesion were considered. Patients who had mediastinal involvement by
148
systemic lymphoma and/or multiple lesions were excluded. Data on tissue sampling techniques
149
such as fine needle aspiration, core biopsy, or surgical resection were not collected. The
150
mediastinum was divided according to the ITMIG classification into prevascular, visceral, and
151
paravertebral compartments as summarized in Supplemental Table 1.[16]
152
The study population included all patients ages 18 years and older. Data on age and
153
gender were also collected. Smoking status was not noted. De-identified data were centrally
154
collected and analyzed.
155
In an attempt to identify differences in the distribution of mediastinal lesions based on
156
geographic areas, the results were combined from hospitals that were from the same continent
157
including Asia, Europe and North America, recognizing that this distribution does not entirely
158
reflect ethnicity and likely is biased by type of institution. Given the large variation in number of
159
cases contributed from the 2 hospitals in Asia, cases from China and Israel were analyzed
160
separately.
161
Data was summarized with frequencies and percentages or with medians, interquartile
162
ranges and ranges (as appropriate). Patient and lesion characteristics were compared by
163
compartment (prevascular vs visceral vs paravertebral), geographic region (China vs Israel vs
164
Europe vs North America), size of hospital (300-600 beds vs > 600 beds), age category (18-29,
165
30-39, 40-49, 50-59, 60-69, ≥ 70) and gender using Kruskal-Wallis tests for age, and Fisher’s
166
exact tests, or chi-square tests for the remaining categorical characteristics. P-values less than
167
0.05 were considered statistically significant. All analyses were performed using SAS version
168
9.4 (SAS Institute Inc., Cary, NC).
169 170 171
Results A total of 3,504 patients with a newly identified mediastinal lesion on CT, PET-CT or
172
MRI scans were identified through the multi-institutional, international database search. Of these
173
patients 196 were excluded because of lack of follow-up imaging and/or pathology. Therefore,
174
3,308 patients were available for the study. Patient demographics are summarized in Table 1.
175
Most lesions were identified by CT scan (Table 1). In approximately two-thirds of patients a
176
pathology diagnosis was available (Table 1), whereas the remainder had typical imaging findings
177
for diagnosis with imaging follow-up for confirmation.
178
Results of Pilot Study
179
To identify optimal search terms two separate pilot searches were performed on radiology
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databases at 4 institutions. One pilot search (broad search criteria) included the following terms:
181
“mediastinal mass”, “mediastinal process”, “mediastinal abnormality”; and cases with a phrase
182
“no mediastinal mass” were excluded. CT, PET/CT and MRI studies were included. This search
183
yielded 421 (Mayo Clinic Rochester, 2012-2015), 3998 (Shanghai Chest Hospital, 2006-2015),
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1484 (MD Anderson, 2012-2015) and 212 (Chaim Sheba, 2012-2015) cases. Between 20 and 27
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cases were reviewed in each hospital to note possible key words; results are summarized in
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Supplemental Table 2. The other pilot search (refined search criteria) was only performed at
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Mayo Clinic Rochester using specific search terms such as “thymoma”, “thymic carcinoma”,
188
“thymolipoma”, “thymic cyst”, “germ cell tumor”, “teratoma”, “lymphangioma”, “parathyroid
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adenoma”, “thyroid goiter”, “pericardial cyst”, “lymphoma”, “metastasis”, “esophageal cancer”,
190
“foregut cyst”, “duplication cyst”, “bronchogenic cyst”, “neurogenic tumor”, “schwannoma”,
191
“neurofibroma”, “ganglioneuroma”, “ganglioneuroblastoma”, “neuroblastoma”, “neurenteric
192
cyst”, “lateral thoracic meningocele”, “sclerosing mediastinitis”, “hemangioma”, and
193
“amyloidosis”. This search generated over 60,000 entries in 2015. This large number of cases
194
occurred because many of these lesions can occur in various organs, not only in the
195
mediastinum. While the use of the refined search criteria might have been more accurate, it was
196
felt that this approach would not have been feasible. Therefore, it was decided to use a variation
197
of the broad search criteria for the final analysis.
198
In addition a search of a pathology database was performed at Mayo Clinic Rochester
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(1995-2014) using the following search terms: “thymus”, “mediastinum”, “vertebra”, and
200
“spine”. This search identified 3,540 (thymus, mediastinum) and 5,182 (vertebra, spine) lesions.
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Four hundred-seventy cases were reviewed of each category. The results (after exclusion of
202
metastases and duplicates) are summarized in Supplemental Table 3.
203 204 205
Overall Frequency of Different Lesions in the Mediastinum The frequency of mediastinal lesions is summarized in Table 1 and illustrated in Figure
206
1A. The entire data are tabulated in Supplemental Table 4. The most common lesions in the
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mediastinum included thymoma, which together with thymic carcinoma constituted 27.8% of
208
mediastinal lesions, benign cysts (20.0%) and lymphomas (16.1%).
209 210
Occurrence of Mediastinal Lesions Based on Mediastinal Compartment
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Most lesions were found to reside within a single mediastinal compartment, with the
212
prevascular mediastinum being the most common site (69.8%) followed by the visceral and
213
paravertebral mediastinum (13.5% and 5.4%, respectively) (Table 1). In 370 (11.2%) patients,
214
the epicenter of the lesion could not be assessed with certainty. In these patients the lesions were
215
attributed to multiple compartments. The majority of the lesions identified in more than 1
216
compartment involved both the prevascular and the visceral compartment (299 of 370) followed
217
by lesions in the visceral and paravertebral (N=48), prevascular, visceral and paravertebral
218
(N=18) and prevascular and paravertebral (N=5) compartments. The frequency of mediastinal
219
lesions based on mediastinal compartment is summarized in Table 1 and Supplement 1. In the
220
prevascular mediastinum, thymomas (30.8%) (Figures 1A and 2A & B) were the most common
221
lesions, followed by benign cysts (24.0%) and lymphomas (14.4%). In contrast, in the visceral
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mediastinum, benign cysts (16.8%) were the predominant lesions (Figure 2C) followed by
223
metastasis (14.8%) and benign thyroid lesions (13.0%). In the paravertebral mediastinum,
224
neurogenic tumors (53.9%) (Figure 2D) were the most often identified lesions, followed by
225
benign cysts (13.9%) and lymphomas (5%).
226
Demographics of Patients Based on Location of Mediastinal Lesion
227
Patient age and gender, based on location of the mediastinal lesion, are summarized in
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Tables 1 and 2 and Figure 1C. The mediastinal compartment in which a lesion was identified
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was associated with the age of the patient (p<0.0001) (Table 1). Patients with lesions in the
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paravertebral compartment were the youngest (median age, 50 years old) while patients with
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visceral mediastinal lesions were the oldest (median age, 60 years old). In contrast, there was no
232
difference in gender amongst different locations of lesions in the mediastinum.
233
Patient age was also associated with the diagnosis (Table 2). For instance, thymomas,
234
thymic carcinomas and benign cysts were most common in the age ranges of 50 to 59 and 60 to
235
69, while lymphomas and germ cell tumors were most frequently found in patients between 18
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and 29 years old.
237
Distribution of Mediastinal Lesions Based on Geographic Region of the Hospital
238
Results of the distribution of mediastinal lesions based on geographic region are
239
summarized in Table 3 and illustrated in Figure 1B. While benign cysts were more common in
240
the group from China (35.5%), followed by thymomas and thymic carcinomas, lymphomas were
241
more common in Israel (24.1%), followed by metastases and thymomas. Metastases were overall
242
most commonly identified in cases from Israel (18.4% of all cases from Israel) (p<0.0001).
243
Cases from Europe were most commonly thymomas (22.8%), followed by lymphomas and
244
benign cysts. In North America, lymphomas were most common (25.5%), followed by
245
thymomas and benign cysts.
246
Frequency of Mediastinal Lesions Based on Size of the Hospital
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The frequencies of mediastinal lesions based on size of the hospital are summarized in
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Table 4. The majority of cases were contributed from larger hospitals with more than 600 beds.
249
None of the participating institutions had less than 300 beds. Relative numbers of paravertebral
250
lesions differed depending on the size of the hospital. Benign cysts, thymic carcinomas, and
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metastases were more commonly seen in larger hospitals, while lymphomas and thymic
252
hyperplasia were found more frequently in smaller hospitals. There was no difference in the
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relative number of patients with thymomas, neurogenic tumors, germ cell tumors, benign thyroid
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lesions and small cell carcinomas depending on the hospital size.
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There were significant differences between the imaging modality that was used to
256
identify the mediastinal lesion between large and smaller hospitals. Most imaging was performed
257
with CT scans. MRI and PET-CT were more frequently used in larger hospitals (4.8% and 3.1%,
258
respectively) than in smaller hospitals (1.8% and 1.2%, respectively).
259 260 261
Discussion In an international, multi-institutional study of solitary mediastinal lesions that were
262
newly identified by CT, PET-CT and/or MRI and collected over a 4-year time period by
263
radiology databases, we found that thymic epithelial malignancies (thymomas and thymic
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carcinomas) are the most common mediastinal lesions (27.8%), followed by benign cysts
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(20.0%), primary mediastinal lymphomas (16.1%) and metastases (5.1%). Furthermore we
266
showed that mediastinal lesions occur in the prevascular compartment most commonly, followed
267
by the visceral compartment. Thymomas were also the most common lesions in the prevascular
268
mediastinum in our study (30.8%), while benign cysts (16.8%) and neurogenic tumors (53.9%)
269
were the most commonly identified lesions in the visceral and paravertebral mediastinum,
270
respectively.
271
Our study has clinical implications, specifically because it was imaging-based and open
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to all adult patients with any available cross-sectional chest imaging. The distribution of the
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different mediastinal lesions found by this investigation will assist in creation of a differential
274
diagnosis when such a patient is encountered in clinic, prior to any surgical intervention or
275
pathology results. This information not only will facilitate development of an informed
276
differential diagnosis, but will also aid in initiating a logical route of continued non-invasive
277
work-up in at least a subset of these patients, justifying the use of different imaging modalities.
278
Although the frequency of mediastinal lesions has been studied in the past, the results
279
were conflicting for reasons that were mentioned earlier. It is difficult to compare our findings to
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previous studies, as these were usually based solely on pathologic and/or surgical databases,
281
were small in size and from a single institution, and/or included cases without a final diagnosis.
282
An example as to how differences between studies substantially affect the distribution of certain
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entities is reflected by the occurrence of a benign mediastinal cyst. In our study based on
284
radiology databases, benign mediastinal cysts were quite common; in fact, benign cysts were the
285
second most common mediastinal lesions (20.0%, after thymomas). They were the most
286
common lesions in the visceral mediastinum (16.8%), and the second most common lesions both
287
in the prevascular mediastinum (24.0%, after thymomas) and in the paravertebral mediastinum
288
(13.9%, after neurogenic tumors). Therefore, benign mediastinal cysts should be placed high on
289
the differential diagnostic list of mediastinal lesions. Similar to our study, in a study from Duke
290
University Medical Center which included 400 consecutive patients with primary mediastinal
291
lesions, all with a pathology diagnosis, 25% of patients were found to have cysts.[9] In contrast,
292
a surgical study of 37 solitary mediastinal masses found only 5 cysts (13.5%) which were
293
comprised of 3 patients with bronchogenic cysts and 2 patients with thymic cysts.[7] It is not
294
surprising that this study had a lower percentage of mediastinal cysts, as it was based on patients
295
who underwent surgical intervention. Knowing that these differences may be reflective of a
296
selection bias of a surgically treated cohort of patients as opposed to our cohort, which was based
297
on imaging studies, it is interesting when compared to two screening CT studies.[2, 3] The study
298
that aimed at screening for lung cancer[3] identified most (41 of 71 cases, 58%) mediastinal
299
lesions as “thymic masses”. Similar to our results, the vast majority of the “thymic masses” (39
300
of 41, 95%) were located in the “anterior” (prevascular) mediastinum. In that study, only 1 of the
301
41 thymic masses was identified as a cyst, 4 were found to be thymomas and 1 was diagnosed as
302
thymic carcinoma. However, in 35 patients with a “thymic mass” a specific diagnosis was not
303
made, and therefore a comparison to our study was difficult. However, in the more recent
304
screening study, which included both smokers and never-smokers, a much greater proportion of
305
benign prevascular cysts was found, more similar to our study. Of the 413 prevascular lesions
306
identified in the screening study, 50 were excised and 12 (24%) were malignant including 11
307
thymic epithelial tumors and 1 non-small-cell lung cancer. The majority of the resected lesions,
308
36 of 50 (72%), were benign cysts. Of these, 32 (89%) were thymic cysts and 4 (11%) were
309
duplication cysts. However, these results are difficult to compare to our study as the majority of
310
the lesions in this study, 362 of 413 prevascular lesions (88%), remained of unknown
311
etiology.[2] Furthermore, our data might be skewed as the majority of thymic cysts were
312
contributed from China. In fact the cohort of mediastinal lesions from China was comprised of
313
significantly more benign cysts (35.5% of all mediastinal lesions) than cohorts from Europe
314
(10.9%), Israel (10.3%), and North America (9.2%). The reason for this difference is not entirely
315
clear and might reflect, at least in part, a selection bias. This is further supported by a previous,
316
albeit much smaller, cohort of patient with mediastinal lesions from a different institution in
317
China that was identified by imaging studies and medical and surgical records and that was
318
comprised only to 15.8% of benign cysts.[17] Furthermore, conceivably, exposures and/or
319
genetic differences might also play a role. However, we did not analyze ethnicity of our study
320
cohort; therefore, these arguments are rather speculative.
321
These conflicting study results regarding the frequency of benign mediastinal cysts is of
322
no surprise, and may in fact reflect the increased use of MRI for thoracic imaging, which has
323
been increasingly recognized for its value.[18] Interestingly, MRI was most commonly used in
324
China (5.4% of all studies) which might, at least partially, explain the relatively high percentage
325
of benign mediastinal cysts in the Chinese cohort. It has been shown that benign mediastinal
326
cysts can be misinterpreted as solid on CT when they are of soft tissue attenuation on account of
327
proteinaceous or hemorrhagic content (up to 97 Hounsfield Units) despite containing fluid alone,
328
which has led in the past to unnecessary surgical resection.[2, 19] It could be that many of the
329
undiagnosed mediastinal masses found in screening for lung cancer patients[3] may have
330
represented such high attenuation cysts. It is possible that the occurrence of mediastinal cysts is
331
far higher than that suggested by our investigation, given the not infrequent under-recognition on
332
CT and the continued underutilization of MRI in many parts of the world. The fact that the use
333
of MRI imaging for chest evaluation has been lagging behind other parts of the body, is only in
334
part due to the motion artifacts inherit to the chest. These artifacts can be overcome with
335
different techniques routinely used today. Reaching clinical decisions by CT images alone,
336
without using MRI, has resulted in many unnecessary surgical procedures for benign disease.[19]
337
The increased use of MRI for evaluation of mediastinal masses is most pronounced in large
338
medical centers, where some clinicians and radiologists with a specific interest in thymomas and
339
MRI, work. Indeed, we noted higher utilization rates of thoracic MRI in larger medical centers as
340
compared to smaller hospitals (4.8% vs 1.8%, respectively). Another explanation might be that
341
MRI scanners are more numerous and more readily accessible in larger centers. Our findings
342
further emphasize that single institution studies might harbor a bias for certain mediastinal
343
lesions, depending on the size of the hospital.
344
We also showed that the occurrence of mediastinal lesions differs with age. For instance,
345
while thymomas, thymic carcinomas, benign cysts, metastases and small cell carcinomas were
346
more commonly identified in patients 50 years and older, lymphomas, germ cell tumors and
347
neurogenic tumors were more often found in patients younger than 50 years old. In fact,
348
lymphomas and germ cell tumors were most commonly seen in patients who were less than 30
349
years old. These findings confirmed previous observations that show median ages of 56[20] and
350
59.6[21] years for thymomas and thymic carcinomas, respectively but a mean age of 29
351
years[22] for mediastinal germ cell tumors.
352
In an attempt to analyze whether certain mediastinal lesions are more commonly seen in
353
larger hospitals, we stratified our results based on the number of beds. As mediastinal lesions are
354
overall rare, it was not surprising that most patients were contributed from larger hospitals with
355
more than 600 beds. None of the participating institutions had less than 300 beds. While this
356
could reflect participation bias, it might also show that these patients were commonly referred to
357
larger hospitals with more expertise in treating these patients.
358
We also showed that the frequency of mediastinal lesions differs depending on the
359
region. While in our study the most common mediastinal lesions overall were thymomas,
360
lymphomas were actually the predominant lesions amongst cases contributed from North
361
America (25.5%) and Israel (24.1%). Furthermore, in China, the relative number of prevascular
362
lesions (83.5%) was higher than in Europe (62.5%), North America (60.8%), and Israel (51.7%),
363
while visceral lesions were much less common in China (5.2%) than in Israel (26.4%), Europe
364
(21.9%) or North America (17.8%). While these findings might be due to referral bias, as all of
365
the cases from China and Israel were contributed from a single hospital, respectively, ethnic
366
differences might also play a role. For instance a study including immigrants with myasthenia
367
gravis in northern Europe showed that myasthenia gravis with thymoma was more frequent in
368
Asian myasthenia gravis immigrants compared with immigrants from Europe and South
369
America.[23] That study concluded that Asian immigrants (in that study from Indonesia, China,
370
Thailand, Vietnam, India, Turkey, Iran, Iraq, and Pakistan) with myasthenia gravis might carry
371
genetic factors or environmental/lifestyle factors that contribute to their specific phenotype.
372
However, we have not collected data specifically on ethnicity from our patients, therefore, a firm
373
conclusion with regards to differences in the frequency of mediastinal lesions based on ethnicity
374
cannot be drawn from our results.
375
While some studies of the incidence of mediastinal lesions avoid the inclusion of
376
lymphomas, our study indicated that lymphomas can occur as a newly diagnosed, single, discrete
377
lesion in the mediastinum. This of course was not reflected in lung cancer screening studies, as
378
such patients do not meet the criteria of inclusion for lung cancer screening studies.[3] Our data
379
highlighted that lymphomas need to be considered in the differential diagnosis of solitary
380
mediastinal lesions. In fact, we showed that lymphomas are the third most common lesion in the
381
mediastinum (16.1%) and although lymphomas can occur in any compartment, these tumors
382
were most often found in the prevascular mediastinum (14.4%) where they represented the third
383
most common lesion after thymomas and benign cysts. Interestingly, lymphomas were most
384
commonly identified in patients from North America (25.5%), followed by Israel (24.1%) and
385
Europe (16.6%) and only 4.9% of all patients from China had lymphomas. Again, the reason for
386
that difference is not clear, and we did not check ethnicity of patients in our study. However, it is
387
known that there are global variations in the incidence of lymphoma. For example, there are
388
marked variations in the incidence rates of NHL in various world regions with Israel Jews having
389
the highest incidence rate of NHL followed by Australia, USA whites, Canada, and Portugal in a
390
recent study of 185 countries using the GLOBOCAN database.[24]
391
There are limitations to our study. (i) Although our study is a multi-institutional,
392
international effort, it solely gathered data from China, Israel, Europe and North America, and
393
lacked contributions from South America, Africa and Australia. Furthermore, a large variety of
394
ethnic groups exist within some of the hospitals studied, in particularly in Europe and North
395
America which could not be assessed due to the retrospective nature of the study. (ii) While over
396
two-thirds of cases had a diagnosis established by pathology, a diagnosis of the remaining
397
patients was established based on imaging investigation and follow-up. (iii) Only lymphomas
398
that presented as a single dominant mediastinal lesion were included, however, conceivably,
399
some of these could have presented as mediastinal involvement by a systemic disease, in a region
400
not included in the imaging study. (iv) The search was performed using the aforementioned 4
401
broad search criteria. The use of these mandated search terms instead of a the refined word
402
search to report lesions may have caused some lesions to escape detection. However, as
403
identified during the pilot study, using refined search terms would have been impractical. (v).
404
While medical records were reviewed for follow-up information and pathology reports,
405
techniques that were used to retrieve the tissue such as FNA, core biopsies or resection was not
406
noted. Therefore, it is difficult to estimate whether potentially pathologic diagnoses could have
407
been missed due to sampling bias in FNAs and core biopsies.
408
Taken together, our multi-institutional, international study of solitary mediastinal lesions
409
based on radiology databases provides an important reference for the frequency and distribution
410
of mediastinal lesions identified on cross-sectional imaging including variance with patient age
411
and geographic region. This information is important when considering the differential diagnosis
412
of a specific patient.
413 414
References
415 416
1.
417 418
Study: Prevalence and CT Image Characteristics. Eur J Radiol Open 2015, 2:26-31. 2.
419 420
Araki T, Nishino M, Gao W, et al: Anterior Mediastinal Masses in the Framingham Heart
Yoon SH, Choi SH, Kang CH, Goo JM: Incidental Anterior Mediastinal Nodular Lesions on Chest CT in Asymptomatic Subjects. J Thorac Oncol 2018, 13:359-366.
3.
Henschke CI, Lee IJ, Wu N, Farooqi A, Khan A, Yankelevitz D, Altorki NK: CT
421
screening for lung cancer: prevalence and incidence of mediastinal masses. Radiology
422
2006, 239:586-590.
423
4.
de Jong WK, Blaauwgeers JL, Schaapveld M, Timens W, Klinkenberg TJ, Groen HJ:
424
Thymic epithelial tumours: a population-based study of the incidence, diagnostic
425
procedures and therapy. Eur J Canc 2008, 44:123-130.
426
5.
Adegboye VO, Brimmo AI, Adebo OA, Ogunseyinde OO, Obajimi MO: The place of
427
clinical features and standard chest radiography in evaluation of mediastinal masses.
428
West Afr J Med 2003, 22:156-160.
429
6.
430 431
Presentation of primary mediastinal masses in Ibadan. East Afr Med J 2003, 80:484-487. 7.
432 433
Adegboye VO, Ogunseyinde AO, Obajimi MO, Ogunbiyi O, Brimmo AI, Adebo OA:
Alizzi AM, Hemli JM, Diqer AM, Bidstrup B: Primary solitary mediastinal mass lesions: a review of 37 cases. Heart Lung Circ 2006, 15:310-313.
8.
Azarow KS, Pearl RH, Zurcher R, Edwards FH, Cohen AJ: Primary mediastinal masses.
434
A comparison of adult and pediatric populations. J Thorac Cardiovasc Surg 1993,
435
106:67-72.
436
9.
Davis RD, Jr., Oldham HN, Jr., Sabiston DC, Jr.: Primary cysts and neoplasms of the
437
mediastinum: recent changes in clinical presentation, methods of diagnosis, management,
438
and results. Ann Thorac Surg 1987, 44:229-237.
439
10.
440 441
of bronchogenic cysts between adults and children. J Pediatr Surg 2015, 50:399-401. 11.
442 443
12.
448
Petersdorf s: Mediastinal lymphomas. In Mediastinal Tumors: Update 1995. Edited by Wood de, Thomas CRJ. New York: Springer-Verlag; 1995
13.
446 447
Rubush JL, Gardner IR, Boyd WC, Ehrenhaft JL: Mediastinal tumors. Review of 186 cases. J Thorac Cardiovasc Surg 1973, 65:216-222.
444 445
Jiang JH, Yen SL, Lee SY, Chuang JH: Differences in the distribution and presentation
Johnson DW, Hoppe RT, Cox RS, Rosenberg SA, Kaplan HS: Hodgkin's disease limited to intrathoracic sites. Cancer 1983, 52:8-13.
14.
Levitt LJ, Aisenberg AC, Harris NL, Linggood RM, Poppema S: Primary non-Hodgkin's lymphoma of the mediastinum. Cancer 1982, 50:2486-2492.
449
15.
450 451
Primary mediastinal lymphoma in adults. Am J Med 1980, 68:509-514. 16.
452 453
Lichtenstein AK, Levine A, Taylor CR, Boswell W, Rossman S, Feinstein DI, Lukes RJ:
Carter BW, Tomiyama N, Bhora FY, et al: A modern definition of mediastinal compartments. J Thorac Oncol 2014, 9:S97-101.
17.
Liu T, Al-Kzayer LFY, Xie X, Fan H, Sarsam SN, Nakazawa Y, Chen L: Mediastinal
454
lesions across the age spectrum: a clinicopathological comparison between pediatric and
455
adult patients. Oncotarget 2017, 8:59845-59853.
456
18.
Ackman JB, Gaissert HA, Lanuti M, Digumarthy SR, Shepard JA, Halpern EF, Wright
457
CD: Impact of Nonvascular Thoracic MR Imaging on the Clinical Decision Making of
458
Thoracic Surgeons: A 2-year Prospective Study. Radiology 2016, 280:464-474.
459
19.
Ackman JB, Verzosa S, Kovach AE, Louissaint A, Jr., Lanuti M, Wright CD, Shepard
460
JA, Halpern EF: High rate of unnecessary thymectomy and its cause. Can computed
461
tomography distinguish thymoma, lymphoma, thymic hyperplasia, and thymic cysts? Eur
462
J Radiol 2015, 84:524-533.
463
20.
Roden AC, Yi ES, Jenkins SM, et al: Modified Masaoka stage and size are independent
464
prognostic predictors in thymoma and modified Masaoka stage is superior to
465
histopathologic classifications. J Thorac Oncol 2015, 10:691-700.
466
21.
Roden AC, Yi ES, Cassivi SD, Jenkins SM, Garces YI, Aubry MC: Clinicopathological
467
features of thymic carcinomas and the impact of histopathological agreement on
468
prognostical studies. Eur J Cardiothorac Surg 2013, 43:1131-1139.
469
22.
Stang A, Trabert B, Wentzensen N, Cook MB, Rusner C, Oosterhuis JW, McGlynn KA:
470
Gonadal and extragonadal germ cell tumours in the United States, 1973-2007. Int J
471
Androl 2012, 35:616-625.
472
23.
473 474
Boldingh MI, Maniaol A, Brunborg C, et al: Prevalence and clinical aspects of immigrants with myasthenia gravis in northern Europe. Muscle Nerve 2016.
24.
Miranda-Filho A, Pineros M, Znaor A, Marcos-Gragera R, Steliarova-Foucher E, Bray F:
475
Global patterns and trends in the incidence of non-Hodgkin lymphoma. Cancer Causes
476
Control 2019, 30:489-499.
477 478 479 480
Figure Legends:
481
Figure 1:
482
compartments. “Other” compartments include lesions that were located in more than one
483
compartment including prevascular and visceral, visceral and paravertebral, prevascular, visceral
484
and paravertebral, and prevascular and paravertebral. Distribution of the most common
485
mediastinal lesions based on geographic areas (B) and age (C). “Other” diagnoses include all
486
diagnoses that are listed in Table 3 except thymoma, benign cyst, lymphoma, thymic carcinoma,
487
and metastasis.
488
Figure 2:
489
in a 53-year-old woman followed for a remote history of Hodgkin lymphoma. A. Contrast
490
enhanced chest CT at the level of the transverse aorta (A) demonstrates a heterogeneous mass
491
(M) in the prevascular mediastinum directly invading the superior vena cava (arrow). B. Fused
492
positron emission tomography–computed tomography (PET-CT) shows there is 68gallium-
493
labelled somatostatin analogue in the mass. C. Esophageal duplication cyst in a 62-year old
494
woman. Unenhanced chest CT shows a 3.7cm homogenous intermediate attenuation mass
495
(arrow) at the level of the left atrium (LA) abutting the esophagus (arrowhead). D. Schwannoma
A. Distribution of the most common mediastinal lesions throughout the different
Example of common mediastinal lesions. A, B. WHO type B2 stage III thymoma
496
in a 34-year old woman. T2 weighted MR image at the level of the sterno-clavicular joint (S)
497
shows a high intensity mass (M) in the paravertebral mediastinum extending into the
498
intervertebral neural foramina (arrow).
499 500
Acknowledgements: Dr. Anja C. Roden would like to thank Robert Dominick for his work on
501
the radiology database.
Table 1: Distribution of mediastinal lesions based on mediastinal compartment (N=3,308)
Mediastinal Compartment, N (%)a
Overall, N (%)
Prevascular
Visceral
Paravertebral
pValuee
N
%
N
%
N
%
N
%
Number of patients
3,308
2,310
446
180
Age in years, median (Q1, Q3)
54.0
54.0
60.0
50.0
(range)
(40.0, 65.0) (40.0, 64.1) (48.0, 70.0) (36.0, 61.0) (18-98)
Gender, maleb
<0.0001
(18-98)
(18-98)
1,676 50.7 1164 50.4 225 50.6
(18-89)
49.4
0.97
92.4 2145 92.9 407 91.3 165 91.7
0.45
89
Imaging modalityf CT
3058
MRI
150
4.5
97
4.2
22
4.9
12
6.7
PET-CT
96
2.9
66
2.9
17
3.8
3
1.7
Pathology diagnosis availablec
2256 68.3 1503 65.1 309 69.4 124 69.3
0.14
Mediastinal lesiond Thymoma
734
22.2
712 30.8
7
1.6
0
0.0
Benign cyst
661
20.0
553 24.0
75
16.8
25
13.9 <0.0001
Lymphoma
532
16.1
333 14.4
34
7.6
9
5.0
<0.0001
Thymic carcinoma
186
5.6
172
1
0.2
0
0.0
<0.0001
7.5
<0.0001
Metastasis
168
5.1
64
2.8
66
14.8
4
2.2
<0.0001
Neurogenic tumor
136
4.1
24
1.0
5
1.1
97
53.9
<0.0001
Germ cell tumor
134
4.1
116
5.0
1
0.2
2
1.1
<0.0001
Benign thyroid lesion
120
3.6
40
1.7
58
13.0
0
0.0
<0.0001
Thymic hyperplasia
91
2.8
90
3.9
0
0.0
0
0.0
<0.0001
Small cell carcinoma
67
2.0
10
0.4
32
7.2
0
0.0
<0.0001
Other
476
14.4
194
8.4
167 37.4
43
23.9
Institutions (by continent and in alphabetical order; size [300-600 beds vs
N
%
1,323
40.0
87
2.6
Hospices Civils de Lyon, France (300-600)
233
7.0
Hôpital Cochin, Paris, France (>600)
164
5.0
Università Degli Studi di Napoli Federico II, Napoli, Italy (>600)
24
0.7
Kingston General Hospital, Ontario, Canada (300-600)
94
2.8
Massachusetts General Hospital, Boston MA, USA (>600)
506
15.3
Mayo Clinic, Rochester MN, USA (>600)
293
8.9
MD Anderson Cancer Center, Houston TX, USA (>600)
337
10.2
NYU Langone Medical Center, New York NY, USA (>600)
120
3.6
Yale School of Medicine, New Haven CT, USA (>600)
127
3.8
>600 beds] is in parentheses) Asia Shanghai Chest Hospital, China (>600) Sheba Medical Center, Ramat Gan, Israel (>600) Europe
North America
Information not available in a2 cases, b1 case, c5 cases, d3 cases, ep-value reflects only difference between prevascular, visceral and paravertebral compartments, Fisher Exact test used for all pvalues except for age for which Kruskal Wallis test was used, f4 other modalities reported besides CT, MRI, PET; these modalities are not included in this table; fields in red mark the entity that is most common in the respective mediastinal compartment.
Table 2: Distribution of mediastinal lesions based on age (N=3,308) p-value a
Age Category (in years) 18-29 N
%b
N
Number of patients
30-39 N
401
Gender, malec
%
40-49 N
424
%
50-59 N
534
%
60-69 N
714
%
≥70 N
681
% 554
221
55.1
232
54.7
254
47.6
336
47.1
356
52.3
277
50
0.029
Mediastinal lesion, N (%)d Thymoma
734
29
7.3
62
14.7
122
22.9
194
27.2
177
26.0
150
27.1 <0.0001
Benign cyst
661
16
4.0
60
14.2
109
20.5
186
26.1
164
24.1
126
22.7 <0.0001
Lymphoma
532
176
44.0 122
28.8
87
16.3
53
7.4
51
7.5
43
7.8
<0.0001
Thymic carcinoma
186
12
3.0
22
5.2
27
5.1
49
6.9
51
7.5
25
4.5
0.020
Metastasis
168
7
1.8
18
4.3
27
5.1
37
5.2
41
6.0
38
6.9
0.012
Neurogenic tumor
136
20
5.0
25
5.9
22
4.1
33
4.6
25
3.7
11
2.0
0.044
Germ cell tumor
134
65
16.3
42
9.9
15
2.8
8
1.1
3
0.4
1
0.2
<0.0001
Benign thyroid lesion
120
1
0.3
3
0.7
9
1.7
23
3.2
33
4.8
51
9.2
<0.0001
Thymic hyperplasia
91
24
6.0
17
4.0
27
5.1
15
2.1
7
1.0
1
0.2
<0.0001
Small cell carcinoma
67
0
0.0
1
0.2
4
0.8
16
2.2
25
3.7
21
3.8
<0.0001
Other
476
50
12.5
51
12.0
84
15.7
100
14.0
104
15.3
87
15.7
a
Chi-Square test; bpercentages are based on column; Information not available in c1 case, d3 cases
Table 3: Distribution of mediastinal lesions based on geographic region (N=3,308) P-Valuea
Geographic region, N (%) China
Israel
N
%
Europe
N
%
N
North America %
N
%
Number of patients
1,323
87
421
1,477
Age in years, median (Q1, Q3) (range)
55.0
53.0
53.3
53.0
(42.0, 64.0)
(34.0, 67.0)
(36.2, 65.2)
(39.0, 66.0)
(18-98)
(21-98)
(18-97.1)
(18-95.9)
Gender, male, N (%)b
0.70
678
51.2
45
52.3
207
49.2
746
50.5
0.88
1250
94.5
75
86.2
400
95.0
1333
90.3
<0.0001
MRI
72
5.4
2
2.3
9
2.1
67
4.5
PET-CT
0
0
10
11.5
12
2.9
74
5.0
691
52.3
50
57.5
353
83.8
1162
78.9
Imaging Modality, N (%) CT
Pathology diagnosis available, N (%)c Mediastinal compartment, N (%)d
<0.0001
Prevascular
1105
83.5
45
51.7
263
62.5
897
60.8
<0.0001
Visceral
69
5.2
23
26.4
92
21.9
262
17.8
<0.0001
Paravertebral
84
6.3
1
1.1
29
6.9
66
4.5
0.02
Multiple compartmentsf
65
4.9
18
20.7
37
8.8
250
16.9
<0.0001
Thymoma
424
32.0
11
12.6
96
22.8
203
13.8
<0.0001
Benign cyst
470
35.5
9
10.3
46
10.9
136
9.2
<0.0001
Lymphoma
65
4.9
21
24.1
70
16.6
376
25.5
<0.0001
Thymic carcinoma
106
8.0
7
8.0
14
3.3
59
4.0
<0.0001
Metastasis
3
0.2
16
18.4
19
4.5
130
8.8
<0.0001
Neurogenic tumor
84
6.3
0
0
16
3.8
36
2.4
<0.0001
Germ cell tumor
72
5.4
1
1.1
8
1.9
53
3.6
0.003
Benign thyroid lesion
29
2.2
2
2.3
13
3.1
76
5.2
0.0004
Thymic hyperplasia
0
0
3
3.4
35
8.3
53
3.6
<0.0001
Small cell carcinoma
1
0.1
2
2.3
5
1.2
59
4.0
<0.0001
Mediastinal lesion, N (%)e
Other a
69
5.2
15
17.2
99
23.5
293
19.8
<0.0001
Fisher Exact or Chi-square test for all except age (Kruskal Wallis test); Information not available in b1 case, c5 cases, d2 cases, e3
cases; fMultiple compartments: Tumors that were present in more than one compartment. See supplement 1 for entire list of tumors; fields in red mark the entity that is most common in the respective mediastinal compartment.
Table 4: Distribution of mediastinal lesions based on size of hospital and type of institution (N=3,308) Size of hospital, N (%) N of Beds 300-600 N
>600 %
p-value
N
%
Number of patients
327
2,981
Age in years, median (Q1, Q3)
52.4
54.0
(34.0, 66.8)
(40.0, 65.0)
(18-97.1)
(18-98)
(range)
Gender, male, N (%)a
0.12e
154
47.1
1,522
51.1
0.18f
317
96.9
2741
91.9
0.011f
MRI
6
1.8
144
4.8
PET-CT
4
1.2
92
3.1
293
89.6
1963
66.0
<0.0001f
Prevascular
215
65.7
2095
70.3
0.10f
Visceral
55
16.8
391
13.1
0.073f
Paravertebral
28
8.6
152
5.1
0.014f
Multiple compartmentsh
29
8.9
341
11.4
Imaging modality, N (%)g CT
Pathology diagnosis available, N (%)b Mediastinal compartment, N (%)c
Mediastinal lesion, N (%)d Thymoma
75
22.9
659
22.1
0.73f
Benign cyst
28
8.6
633
21.3
<0.0001f
Lymphoma
72
22.0
460
15.4
0.0032f
Thymic carcinoma
6
1.8
180
6.0
0.0009f
Metastasis
5
1.5
163
5.5
0.0008f
Neurogenic tumor
8
2.4
128
4.3
0.14f
Germ cell tumor
9
2.8
125
4.2
0.24f
Benign thyroid lesion
14
4.3
106
3.6
0.53f
Thymic hyperplasia
18
5.5
73
2.5
0.0036f
Small cell carcinoma
2
0.6
65
2.2
0.060f
Others
90
27.5
386
12.9
Information not available in a1 case, b5 cases, c2 cases; d3 cases, eKruskal Wallis test, fFisher Exact test, gOther imaging modality in 4 cases in institutions with >600 beds; hMultiple compartments: Tumors that were present in more than one compartment. See supplement 1 for entire list of tumors; fields in red mark the entity that is most common in the respective mediastinal compartment.